Expression and Clinical Significance of Transforming Growth Factorbeta1 (TGFbeta1) and TGFbeta ReceptorII in Pancreatic Cancer and in Chronic Pancreatitis

Han, Chan Hong; Kim, Jung Taek

Abstract

PURPOSE: Transforming growth factorbeta (TGFbeta) is an extracellular ligand that binds to a heterodimeric receptor, initiating signals that regulate growth, differentiation, and apoptosis. Many cancers, including pancreatic cancer, harbor defects in TGFbeta signaling and are resistant to TGFbeta-mediated growth inhibition. Recently, it has been reported that enhanced expression of TGFbeta1 is associated with the progression of a pancreatic ductal cell carcinoma (PCA) and chronic pancreatitis (CP). We investigated the difference in the expressions of TGFbeta1 and the TGFbeta receptor II (TbetaRII) in PCA and CP and the clinical significance of TGFbeta1 and TbetaRII in PCA. METHODS: Surgically resected pancreatic specimen were obtained from 26 patients with a PCA and 12 with CP; 5 normal pancreatic tissue specimens were also obtained. The specimens were immunostained for TGFbeta1 and TbetaRII. RESULTS: Immunohistochemical analyses of TGFbeta1 and TbetaRII revealed positive immunostaining in 73.1% and 66.7% of the tumors, respectively. In the ductal epithelial cells of PCA and CP, there were no significant differences in the expressions of TGFbeta1 and TbetaRII. In contrast, their stromal expressions tended to be stronger in PCA than in CP; especially, the expression of TbetaRII was significantly higher in PCA (p=0.008). Also the presence of TGFbeta1 and TbetaRII in the cancer was significantly associated with node metastasis, advanced tumor stage (p<0.01), and short survival time (p<0.05). CONCLUSION: There might be some pathological difference in the stromal reactions of TGFbeta1 or TbetaRII between PCA and CP. The presence of TGFbeta1 or TbetaRII indicates a role in disease progression.